EFFECTS OF THE LIPASE INHIBITOR ORLISTAT ON INTAKE AND PREFERENCE FORDIETARY-FAT IN RATS

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat-source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to-adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake an d increasing their protein and carbohydrate intake in a dose-related m anner. Total caloric intake also increased, but body weight gain was i nhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight re turned to control levels. In additional short-term experiments (30 min /day), rats developed a preference for a plain fat diet over an Ols-fa t diet (4 mg/g fat) and also for a cue flavor paired with plain fat ov er a flavor paired with Ols-fat. Yet, when not given the choice, the r ats consumed nearly as much Ols-fat as plain fat diet. These results i ndicate that, by reducing fat absorption, Ols reduced the attractivene ss of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary f at intake by reducing both the consumption and absorption of fat.